tbuckley/cabot-search huggingface dataset:
Acute myeloid leukemia as an adverse event in a patient treated with a poly(ADP‐ribose) polymerase (PARP) inhibitor
Authors: Sandrine Girard, Camille Lours
Journal: American Journal of Hematology (2023)

A 57-year-old woman with a history of breast cancer (17 years earlier) and high-grade serous ovarian adenocarcinoma (9 years earlier) with germline variation of BRCA1 was admitted for exploration of severe pancytopenia (WBC 0.86 × 109/L, Hb 58 g/L, Plt 14 × 109/L). She received olaparib (PARP inhibitor) treatment for 4 years. Peripheral blood smear revealed erythroid-like blasts (11%), nucleated RBCs (4/100 WBC), dysplastic neutrophils (abnormal chromatin clumping, nuclear hyperchromasia, cytoplasmic hypogranularity) and abnormally large or hypogranulated platelets. Bone marrow aspirate smear showed hypercellularity with 65% erythroid-like blasts (mainly large with deeply basophilic cytoplasm, rarely vacuolated, round nuclear contours, scattered chromatin) and 5% undifferentiated blasts (more abundant and rarely slightly granular cytoplasm, prominent nucleoli) (Image 1). Marked trilineage dysplasia was found. Flow cytometric analysis confirmed blastic infiltration (~70%), mostly (65%) of erythroid lineage (CD34−,CD38++,CD36+,CD71+ CD13−,CD33− CD117+dim), and 5% myeloblastic, minimally differentiated (CD34+,CD38+/−,CD36−,CD13++,CD117++,CD33+/−,CD56+/−), confirming the morphological assessment. Cytogenetic analysis found a complex karyotype: 44,XX,del(5)(q12q35),der(7)t(7;13)(q31;q14),−13,−18,−19,add(21)(p11),+mar[20] and molecular analysis TP53 variation (p.Cys275Tyr; VAF 85%). These results are in agreement with the pathological and genetic characteristics of acute myeloid leukemias in patients treated with PARP inhibitors1, 2: complex karyotypes involving chromosomes 5 and 7, frequent recurrence of TP53 variations, and frequent morphological features of pure erythroid leukemia. PARP inhibitors are widely used in the treatment of neoplasia, particularly in patients with BRCA germline variations. They have recently been found to increase in about 1%–2% of patients, the risk of developing secondary myelodysplastic syndrome and/or acute myeloid leukemia.3 This research received no specific grants from any funding agency. The authors declare no conflicts of interests relating to the submitted publication. The patient gives her permission to use clinical information and images relating to the publication. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials
Authors: Malgorzata K. Nowakowska, Rachel M. Ortega, Mackenzie R. Wehner, Kevin T. Nead
Journal: JAMA Oncology (2023)

Importance The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed. Objective To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects. Data Sources PubMed, EMBASE, and Scopus (inception to September 12, 2022). Study Selection Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, fatigue, weakness), or falls were evaluated. Data Extraction and Synthesis Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Enhancing the Quality and Transparency of Health Research reporting guidelines. Tabular counts for all-grade toxic effects were determined to test the hypothesis formulated before data collection. Main Outcomes and Measures Risk ratios (RRs) and SEs were calculated for cognitive toxic effects, asthenic toxic effects, and falls. Because fatigue was the asthenic toxic effect extracted from all studies, data on fatigue are specified in the results. Meta-analysis and meta-regression were used to generate summary statistics. Results The systematic review included 12 studies comprising 13 524 participants. Included studies had a low risk of bias. An increased risk of cognitive toxic effects (RR, 2.10; 95% CI, 1.30-3.38; P = .002) and fatigue (RR, 1.34; 95% CI, 1.16-1.54; P &amp;amp;lt; .001) was noted among individuals treated with second-generation AAs vs those in the control arms. The findings were consistent in studies that included traditional hormone therapy in both treatment arms for cognitive toxic effects (RR, 1.77; 95% CI, 1.12-2.79; P = .01) and fatigue (RR, 1.32; 95% CI, 1.10-1.58; P = .003). Meta-regression supported that, across studies, increased age was associated with a greater risk of fatigue with second-generation AAs (coefficient, 0.75; 95% CI, 0.04-0.12; P &amp;amp;lt; .001). In addition, the use of second-generation AAs was associated with an increased risk of falls (RR, 1.87; 95% CI, 1.27-2.75; P = .001). Conclusions and Relevance The findings of this systematic review and meta-analysis suggest that second-generation AAs carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.
Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry
Authors: Sarah Abou Alaiwi, Thomas M. Roston, Peter Marstrand, Brian Lee Claggett, Victoria N. Parikh, Adam S. Helms, Jodie Ingles, Rachel Lampert, Neal K. Lakdawala, Michelle Michels, Anjali T. Owens, Joseph W. Rossano, Sara Saberi, Dominic J. Abrams, Euan A. Ashley, Christopher Semsarian, John C. Stendahl, James S. Ware, Erin Miller, Thomas D. Ryan, Mark W. Russell, Sharlene M. Day, Iacopo Olivotto, Christoffer R. Vissing, Carolyn Y. Ho
Journal: Circulation (2023)

The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.
The skin of people experiencing homelessness: more (known) is less (neglected)
Authors: Olivier Chosidow, Aileen Y Chang
Journal: British Journal of Dermatology (2023)

Journal Article The skin of people experiencing homelessness: more (known) is less (neglected) Get access Olivier Chosidow, Olivier Chosidow AP-HP, Hôpital Pitié-Salpêtrière, Facial Dermatosis Clinic, and Paris-Est University, 94010 Créteil, FranceGrIDIST (Infectious skin diseases and STI working group), French Society of Dermatology, Paris, FranceCommunity Dermatology Committee, International Society of Dermatology, New Orleans, LA, USA Correspondence: Olivier Chosidow. Email: olivier.chosidow@aphp.fr https://orcid.org/0000-0002-8400-4310 Search for other works by this author on: Oxford Academic Google Scholar Aileen Y Chang Aileen Y Chang University of California San Francisco, Department of Dermatology, San Francisco, CA, USAZuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA, USA https://orcid.org/0000-0002-4921-2333 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 6, June 2023, Pages 694–695, https://doi.org/10.1093/bjd/ljad088 Published: 24 May 2023 Article history Received: 15 March 2023 Published: 24 May 2023
Letter to the Editor: Acute rejection after liver transplantation with machine perfusion versus static cold storage: A systematic review and meta-analysis
Authors: Aijun Liang, Junjun Jia, Kebo Zhong, Yu Nie
Journal: Hepatology (2023)

1Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Province, Hangzhou 310003, China Funding: None. Correspondence Yu Nie MD, Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Email: [email protected]
Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism
Authors: DuoYao Cao, Zakir Khan, Xiaomo Li, Suguru Saito, Ellen A Bernstein, Aaron R Victor, Faizan Ahmed, Aoi O Hoshi, Luciana C Veiras, Tomohiro Shibata, Mingtian Che, Lei Cai, Michifumi Yamashita, Ryan E Temel, Jorge F Giani, Daniel J Luthringer, Ajit S Divakaruni, Derick Okwan-Duodu, Kenneth E Bernstein
Journal: Cardiovascular Research (2023)

Abstract Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis. Methods and results Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of lipid, increased capacity to transport long chain fatty acids into mitochondria, higher oxidative metabolism and lipid β-oxidation as determined using 13C isotope tracing, increased cell ATP, increased capacity for efferocytosis, increased concentrations of the lipid transporters ABCA1 and ABCG1, and increased cholesterol efflux. These effects are mostly independent of angiotensin II. Human THP-1 cells, when modified to express more ACE, increase expression of PPARα, increase cell ATP and acetyl-CoA, and increase cell efferocytosis. Conclusion Increased macrophage ACE expression enhances macrophage lipid metabolism, cholesterol efflux, efferocytosis, and it reduces atherosclerosis. This has implications for the treatment of cardiovascular disease with angiotensin II receptor antagonists vs. ACE inhibitors.
Carbon monoxide as a clinical marker of hemolysis
Authors: Jake Osborne, Mohamad Sobh, Guy Trudel
Journal: American Journal of Hematology (2023)

Abstract Carbon monoxide (CO)‐based tests have precisely measured hemolysis for over 40 years. End‐tidal CO was the primary marker in clinical hematology research, followed by carboxyhemoglobin. Quantification of CO reflects heme oxygenases degrading heme in a 1:1 stoichiometric ratio, making CO a direct marker of hemolysis. CO in alveolar air can be quantified using gas chromatography, whose high resolution allows detecting mild and moderate levels of hemolysis. CO can be elevated in active bleeding, resorbing hematoma, and smoking. Clinical acumen and other markers remain necessary to diagnose the cause of hemolysis. CO‐based tests constitute an opportunity for bench‐to‐bedside technology transfer.
Comprehensive surveillance of acute respiratory infections during the COVID-19 pandemic: a methodological approach using sentinel networks, Castilla y León, Spain, January 2020 to May 2022
Authors: Tomás Vega-Alonso, Jose Eugenio Lozano-Alonso, Ana Ordax-Díez
Journal: Eurosurveillance (2023)

BackgroundSince 1996, epidemiological surveillance of acute respiratory infections (ARI) in Spain has been limited to seasonal influenza, respiratory syncytial virus (RSV) and potential pandemic viruses. The COVID-19 pandemic provides opportunities to adapt existing systems for extended surveillance to capture a broader range of ARI.AimTo describe how the Influenza Sentinel Surveillance System of Castilla y León, Spain was rapidly adapted in 2020 to comprehensive sentinel surveillance for ARI, including influenza and COVID-19.MethodsUsing principles and methods of the health sentinel network, we integrated electronic medical record data from 68 basic surveillance units, covering 2.6% of the regional population between January 2020 to May 2022. We tested sentinel and non-sentinel samples sent weekly to the laboratory network for SARS-CoV-2, influenza viruses and other respiratory pathogens. The moving epidemic method (MEM) was used to calculate epidemic thresholds.ResultsARI incidence was estimated at 18,942 cases per 100,000 in 2020/21 and 45,223 in 2021/22, with similar seasonal fold increases by type of respiratory disease. Incidence of influenza-like illness was negligible in 2020/21 but a 5-week epidemic was detected by MEM in 2021/22. Epidemic thresholds for ARI and COVID-19 were estimated at 459.4 and 191.3 cases per 100,000 population, respectively. More than 5,000 samples were tested against a panel of respiratory viruses in 2021/22.ConclusionExtracting data from electronic medical records reported by trained professionals, combined with a standardised microbiological information system, is a feasible and useful method to adapt influenza sentinel reports to comprehensive ARI surveillance in the post-COVID-19 era.
Start Mammograms at 40, Not 50, USPSTF Suggests
Journal: Cancer Discovery (2023)

The U.S. Preventive Services Task Force has proposed changing the recommended age for women to begin getting routine breast cancer screenings from 50 to 40. In new draft recommendations, the task force says the shift was driven by new data showing persistent racial disparities in breast cancer death rates, as well as rising diagnoses among younger women.
Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study
Authors: Nana Owusu-Boaitey, Timothy W Russell, Gideon Meyerowitz-Katz, Andrew T Levin, Daniel Herrera-Esposito
Journal: Eurosurveillance (2023)

BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.
Reassessing the survival benefit of deceased donor liver transplantation: retrospective cohort study
Authors: John S. Malamon, Bruce Kaplan, Whitney E. Jackson, Jessica L. Saben, Jesse D. Schold, Elizabeth A. Pomfret, James J. Pomposelli
Journal: International Journal of Surgery (2023)

Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing's 'Share-15' policy states that candidates with MELD-Na scores of 15 or greater have priority to receive local organ offers compared to candidates with lower MELD-Na scores. Since the inception of this policy, major changes in the primary etiologies of end-stage liver disease have occurred and previous assumptions need to be recalibrated.The authors retrospectively analyzed the Scientific Registry of Transplant Recipients database between 2012 and 2021 to determine life years saved by DDLT at each interval of MELD-Na score and the time-to-equal risk and time-to-equal survival versus remaining on the waitlist. The authors stratified our analysis by MELD exception points, primary disease etiology, and MELD score.On aggregate, compared to remaining on the waitlist, a significant 1-year survival advantage of DDLT at MELD-Na scores as low as 12 was found. The median life years saved at this score after a liver transplant was estimated to be greater than 9 years. While the total life years saved were comparable across all MELD-Na scores, the time-to-equal risk and time-to-equal survival decreased exponentially as MELD-Na scores increased.Herein, the authors challenge the perception as to the timing of DDLT and when that benefit occurs. The national liver allocation policy is transitioning to a continuous distribution framework and these data will be instrumental to defining the attributes of the continuos allocation score.
Error in the Role of the Funder/Sponsor Section
Journal: JAMA Network Open (2023)

Tara Kiran, MD, MSc; Michael E. Green, MD, MPH; Rachel Strauss, MPH; C. Fangyun Wu, MSc, MA; Maryam Daneshvarfard, MScCH; Alexander Kopp, BA; Lauren Lapointe-Shaw, MD, PhD; Lidija Latifovic, MSc; Eliot Frymire, MA, BEd; Richard H. Glazier, MD, MPH
The artificial intelligence and machine learning in lung cancer immunotherapy
Authors: Qing Gao, Luyu Yang, Mingjun Lu, Renjing Jin, Huan Ye, Teng Ma
Journal: Journal of Hematology & Oncology (2023)

Abstract Since the past decades, more lung cancer patients have been experiencing lasting benefits from immunotherapy. It is imperative to accurately and intelligently select appropriate patients for immunotherapy or predict the immunotherapy efficacy. In recent years, machine learning (ML)-based artificial intelligence (AI) was developed in the area of medical-industrial convergence. AI can help model and predict medical information. A growing number of studies have combined radiology, pathology, genomics, proteomics data in order to predict the expression levels of programmed death-ligand 1 (PD-L1), tumor mutation burden (TMB) and tumor microenvironment (TME) in cancer patients or predict the likelihood of immunotherapy benefits and side effects. Finally, with the advancement of AI and ML, it is believed that "digital biopsy" can replace the traditional single assessment method to benefit more cancer patients and help clinical decision-making in the future. In this review, the applications of AI in PD-L1/TMB prediction, TME prediction and lung cancer immunotherapy are discussed.
Interim 2022/23 influenza vaccine effectiveness: six European studies, October 2022 to January 2023
Authors: Esther Kissling, Marine Maurel, Hanne-Dorthe Emborg, Heather Whitaker, Jim McMenamin, Jennifer Howard, Ramona Trebbien, Conall Watson, Beth Findlay, Francisco Pozo, Amanda Bolt Botnen, Ciaran Harvey, Angela Rose
Journal: Eurosurveillance (2023)

Background Between October 2022 and January 2023, influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe with different influenza (sub)types dominating in different areas. Aim To provide interim 2022/23 influenza vaccine effectiveness (VE) estimates from six European studies, covering 16 countries in primary care, emergency care and hospital inpatient settings. Methods All studies used the test-negative design, but with differences in other study characteristics, such as data sources, patient selection, case definitions and included age groups. Overall and influenza (sub)type-specific VE was estimated for each study using logistic regression adjusted for potential confounders. Results There were 20,477 influenza cases recruited across the six studies, of which 16,589 (81%) were influenza A. Among all ages and settings, VE against influenza A ranged from 27 to 44%. Against A(H1N1)pdm09 (all ages and settings), VE point estimates ranged from 28% to 46%, higher among children (&lt; 18 years) at 49–77%. Against A(H3N2), overall VE ranged from 2% to 44%, also higher among children (62–70%). Against influenza B/Victoria, overall and age-specific VE were ≥ 50% (87–95% among children &lt; 18 years). Conclusions Interim results from six European studies during the 2022/23 influenza season indicate a ≥ 27% and ≥ 50% reduction in disease occurrence among all-age influenza vaccine recipients for influenza A and B, respectively, with higher reductions among children. Genetic virus characterisation results and end-of-season VE estimates will contribute to greater understanding of differences in influenza (sub)type-specific results across studies.
2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis
Authors: Bryant R. England, Benjamin J. Smith, Nancy A. Baker, Jennifer L. Barton, Carol A. Oatis, Gordon Guyatt, Allen Anandarajah, Kristine Carandang, Karmela Kim Chan, Deb Constien, Eileen Davidson, Carole V. Dodge, Anita Bemis‐Dougherty, Sotiria Everett, Nadine Fisher, Liana Fraenkel, Susan M. Goodman, Janet Lewis, Victoria Menzies, Larry W. Moreland, Iris Navarro‐Millan, Sarah Patterson, Lawrence “Rick” Phillips, Neha Shah, Namrata Singh, Daniel White, Rawan AlHeresh, Kamil E. Barbour, Thomas Bye, Dana Guglielmo, Rebecca Haberman, Tate Johnson, Anatole Kleiner, Chris Y. Lane, Linda C. Li, Hiral Master, Daniel Pinto, Janet L. Poole, Kimberly Steinbarger, Daniel Sztubinski, Louise Thoma, Vlad Tsaltskan, Marat Turgunbaev, Courtney Wells, Amy S. Turner, Jonathan R. Treadwell
Journal: Arthritis & Rheumatology (2023)

To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA).
Zavegepant: First Approval
Authors: Sohita Dhillon
Journal: Drugs (2023)

Zavegepant is a third generation, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by Pfizer, under a license from Bristol-Myers Squibb, for the prevention and treatment of chronic and episodic migraine. In March 2023, zavegepant nasal spray (ZAVZPRET™) received its first approval in the USA for the acute treatment of migraine with or without aura in adults. Clinical development of an oral formulation of zavegepant is currently underway. This article summarizes the milestones in the development of zavegepant leading to this first approval for the acute treatment of migraine with or without aura in adults.
Hand eczema leaves systemic traces
Authors: Lennart M Roesner, Miriam Wittmann
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Hand eczema leaves systemic traces Get access Lennart M Roesner, Lennart M Roesner Department of Dermatology and Allergy, Hannover Medical School, Hannover, GermanyCluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany Correspondence: Lennart M. Roesner, Email: roesner.lennart@mh-hannover.de Search for other works by this author on: Oxford Academic Google Scholar Miriam Wittmann Miriam Wittmann University Medical Center of the Johannes Gutenberg-University of Mainz, Department of Dermatology, Mainz, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad178, https://doi.org/10.1093/bjd/ljad178 Published: 24 May 2023 Article history Received: 17 May 2023 Revision received: 22 May 2023 Accepted: 22 May 2023 Published: 24 May 2023